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Maternal High-Fat Diet Aggravates Allergic Asthma in Offspring via Modulating CD4+ T-Cell Differentiation
Hui Lin1,2,3, Yiran Zhao2,3,4, Yajie Zhu2,3,4
1Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai 200011, China.
Insights
Maternal high-fat diet during pregnancy exacerbates allergic asthma in offspring by altering CD4+ T-cell immune responses. These early life nutritional changes can lead to long-term epigenetic modifications and increased allergy risk.
Area of Science:
- Immunology
- Developmental Biology
- Nutritional Science
Background:
- Maternal nutrition significantly impacts offspring health, with improper nutrition linked to respiratory disorders.
- The fetal environment plays a critical role in immune system development and long-term health outcomes.
Purpose of the Study:
- To investigate the effects of a maternal high-fat diet (HFD) during gestation on offspring susceptibility to allergic asthma.
- To characterize the impact of maternal HFD on CD4+ T-lymphocytes in mice and humans.
- To explore the underlying epigenetic mechanisms contributing to altered immune responses.
Main Methods:
- Established an experimental asthma model in mice offspring of mothers on HFD.
- Collected human cord blood from neonates of hypercholesterolemic (HC) and control mothers.
- Analyzed CD4+ T-cell activation, proliferation, gene expression (klf2, Il-4), and DNA methylation patterns.
- Assessed T-cell immune responses in vivo and in vitro.
- Correlated findings with allergic disease development in human offspring at 3 years old.
Main Results:
- Maternal HFD aggravated airway hyperresponsiveness and inflammation in adult offspring mice.
- Offspring CD4+ T-cells exhibited augmented activation and proliferation, potentially involving upregulated klf2.
- Naïve CD4+ T-cells from HFD offspring showed enhanced T H 2 immune responses due to Il-4 promoter hypomethylation.
- Human cord blood CD4+ T-cells from HC mothers displayed enhanced T H 2 cytokine transcripts.
- Enhanced T H 2 responses in human cord blood T-cells were associated with increased allergy risk at age 3.
Conclusions:
- Maternal high-fat diet during fetal development can lead to exacerbated allergic asthma in offspring.
- Epigenetic modifications, specifically DNA hypomethylation of the Il-4 promoter in CD4+ T-cells, are implicated in the enhanced T H 2 response.
- Early life improper nutrition can induce lasting epigenetic alterations in T-cells, contributing to long-term susceptibility to allergic diseases.
Abstract:
Maternal improper nutrition has been reported to trigger respiratory disorders in offspring. Here, we characterized the effects of high-fat environment in the fetal period on mice and human cord blood CD4+ T-lymphocytes, and investigated their roles in susceptibility to asthma. Mice born to mothers that consumed a high-fat diet (HFD) throughout the gestation period were sensitized by ovalbumin to establish an experimental asthma model. To further extrapolate to humans, we collected cord blood from neonates of hypercholesterolemic (HC) mothers (n = 18) and control mothers (n = 20). In mice, aggravated airway hyperresponsiveness and inflammation revealed that maternal high-fat diet could lead to exacerbated allergic asthma in adult offspring. It was partially due to augmented activation and proliferation of CD4+ T-cells, where upregulated klf2 mRNA levels may be potentially involved. Notably, naïve HFD CD4+ T-cells had enhanced TH2-based immune response both in vivo and in vitro, resulting from DNA hypomethylation of the Il-4 promoter region. Moreover, in human, TH2 cytokines transcripts were enhanced in CD4+ T-cells of the HC group, which was associated with an increased risk of developing allergic diseases at 3 years old. Together, our study indicated that early life improper nutrition-triggered epigenetic changes in T-cells may contribute to long-lasting alterations in allergic diseases.
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